偶氮染料及其代谢产物的化学结构与毒性关系的回顾与前瞻

Review of the Mutagenicity,Carcinogenicity and Autoimmunity of Azo Dyes and their Metabolites from the Perspective of their Structure-activity Relationships

偶氮染料用途广泛。当它们进入人体后 ,会被肠道细菌的偶氮还原酶分解成芳香胺。许多食物因子会影响偶氮还原酶的活性。许多芳香胺具有致突变性和致癌性。作者发现只有在分子结构上含有对苯二胺(p_phenylenediamine)或联苯胺(benzidine)的偶氮染料才会因代谢而具有致突变性或致癌性。因此 ,对苯二胺和联苯胺便是偶氮染料之主要致突变成分。这类芳香胺都需要代谢活化才能表现其致突变性。如在其分子结构上多加一个亚硝基(_NO2)或氯基(_Cl) ,会使其变为直接诱变剂。在苯环上如有甲基(_CH 3)或胺基(_NH 2)也会影响这些芳香胺的致突变力。分子轨道能如thehighestoccupiedmolecularorbitalenergy(E HOMO),thelowestunoccupiedmolecularorbitalenergy(ELUMO) ,和亲脂性与致突变力有直接相关性。突变性芳香胺会被代谢活化成为高活性的亲电子产物与DNA结合成DNA加合物而诱发突变。这些芳香胺也可能被氧化产生自由基 ,进而再与体内物质代谢产生一系列的活性氧 (ROS)。ROS攻击DNA造成DNA之氧化损伤而发生突变。作者推测有些芳香胺也可能被代谢活化后与DNA相互吸引 ,诱导DNA从正常的“B”态变成有抗原性的“Z”态 ,因而引发体内的“B”细胞产生抗体与本身之DNA或其核内的成分形成一种免疫复合物 ,堆积于微血管引发?

Azo dyes are widely used in various industries.When azo dyes enter into the human body,they can be reductively cleaved into aromatic amines by azo reductase of intestinal bacteria.Various dietary factors affect the azo reductase activity in the gastrointestinal tract.Many aromatic amines are mutagenic and/or carcinogenic.Azo dyes that contain either p-phenylenediamine or benzidine in the molecules will become mutagenic/carcinogenic after azo reduction.Therefore,p-phenylenediamine and benzidine appear to be the muˉtagenic moieties of these azo dyes.These mutagenic amines require metabolic activation for mutagenicity.However,the addition of a nitro-group or a halogen group to the amines convert them into direct mutagens.Various functional groups(i.e.NO 2 ,CH 3 ,and NH 2 )within the molecules of these amines also affect their mutagenic potencies.Among the various physicochemical properties of these amines examined,the molecular orbital energies such as the lowest unoccupied molecular orbital energy(E LUMO )and the highest occupied molecular orbital energy(E HOMO ),and hydrophobicity are correlated with their mutagenic potencies.These mutagenic amines may be metabolically activated to active electrophilic metabolites,which can interact with deoxyribonucleic acid(DNA)to produce DNA adducts in order to cause mutations.These aromatic amines can also be peroxidatively metabolized to generate free radicals that can interact with oxygen to produce superoxide anions.These superoxide anions can ultimately generate hydroxy radicals and the associated reactive oxygen species(ROS),which attack DNA and cause oxidative DNA damage,resulting in mutagenesis.Some of the aromatic amines(including non-mutagenic and mutagenic)may also be metabolically activated to produce active intermediates,which interact with DNA to cause the DNA to convert from B form into Z form.The Z form DNA can work as an immunogen and can induce the forˉmation of antibodies,which act against body DNA and other nuclear components and form immune complexes in small blood vessels.Therefores,some of these aromatic amines may cause autoimmune diseases such as drug induced lupus(DIL),systemic lupus erytheˉmatosus(SLE)and rheumatoid arthritis.